DMBA-induced mammary pathologies are angiogenic in vivo and in vitro

We have previously shown that human pre-invasive diseases of the breast are angiogenic. In addition, normal epithelium from women with coincident or s ubsequent invasive breast cancer is more vascular than normal epithelium fr om women with no breast cancer. To develop a model in which to study the re gulation of angiogenesis in pre-invasive mammary pathologies, we examined 7 ,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tissues for the pr esence of neovascularization in pre-invasive histopathologies. These studie s included morphometric analysis of tissue vascularity in pre-invasive lesi ons. In addition, we isolated fresh tumors and histologically normal epithe lium (organoids) from DMBA or vehicle-treated control rats to test their ab ility to induce endothelial cell tubule formation in vitro. Finally, we exa mined tumors for their ability to produce vascular endothelial cell growth factor. The morphometric studies documented that with epithelial progressio n, the ability of individual cells to elicit angiogenesis increases. The in vitro studies showed that isolated tumors from these animals stimulate ang iogenesis. Furthermore, normal epithelium from DMBA-treated rats is more an giogenic than epithelium from control animals. Finally, DMBA-induced tumors produce vascular endothelial growth factor (VEGF) mRNA, therefore, DMBA-in duced mammary tumorigenesis is one model in which to test the dependency of progression on angiogenesis.